Background The objective of this study was to investigate the effects of reduction, cessation, and resumption of smoking on cancer development. Methods The authors identified 893,582 participants who currently smoked, had undergone a health screening in 2009, and had a follow-up screening in 2011. Among them, 682,996 participated in a third screening in 2013. Participants were categorized as quitters, reducers I (≥50% reduction), reducers II (<50% reduction), sustainers (referent), or increasers (≥20% increase). Outcome data were obtained through December 31, 2018. Results Reducers I exhibited a decreased risk of all cancers (adjusted hazard ratio [aHR], 0.96; 95% confidence interval [CI], 0.93-0.99), smoking-related cancers (aHR, 0.95; 95% CI, 0.92-0.99), and lung cancer (aHR, 0.83; 95% CI, 0.77-0.88). Quitters had the lowest risk of all cancers (aHR, 0.94; 95% CI, 0.92-0.96), smoking-related cancers (aHR, 0.91; 95% CI, 0.89-0.93), and lung cancer (aHR, 0.79; 95% CI, 0.76-0.83). In further analysis with 3 consecutive screenings, additional smoking reduction (from reducers II to reducers I) lowered the risk of lung cancer (aHR, 0.74; 95% CI, 0.58-0.94) in comparison with sustainers. Quitting among reducers I further decreased the risk of all cancers (aHR, 0.90; 95% CI, 0.80-1.00), smoking-related cancers (aHR, 0.81; 95% CI, 0.81-0.92), and lung cancer (aHR, 0.66; 95% CI, 0.52-0.84) in comparison with sustainers. Smoking resumption after quitting, even at a lower level, increased the risk of smoking-related cancers (aHR, 1.19; 95% CI, 1.06-1.33) and lung cancer (aHR, 1.48; 95% CI, 1.21-1.80) in comparison with sustained quitting. Conclusions Smoking cessation and, to a lesser extent, smoking reduction decreased the risks of cancer. Smoking resumption increased cancer risks in comparison with sustained quitting.